Vascular Anomalies

Adams, Denise M.; Ricci, Kiersten

doi:10.1016/j.hoc.2019.01.011

Cited by 71 publications

(37 citation statements)

References 86 publications

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“…In initially making a clinical CLOVES diagnosis for our patient, a trial of oral sirolimus treatment was undertaken. An mTOR inhibitor approved as an immunosuppressant in transplant patients, discovery of the PI3K/AKT/mTOR pathway’s role in LM, VM, and associated overgrowth syndromes led to sirolimus being used as a palliative treatment for a severe vascular anomaly in a child, with resultant decreased anomaly size [4]. Numerous studies but few trials have been reported since, and only one report of an NRAS mutation VM showing a response to sirolimus exists [4, 14].…”

Section: Discussionmentioning

confidence: 99%

“…An mTOR inhibitor approved as an immunosuppressant in transplant patients, discovery of the PI3K/AKT/mTOR pathway’s role in LM, VM, and associated overgrowth syndromes led to sirolimus being used as a palliative treatment for a severe vascular anomaly in a child, with resultant decreased anomaly size [4]. Numerous studies but few trials have been reported since, and only one report of an NRAS mutation VM showing a response to sirolimus exists [4, 14]. Recent reports note sirolimus is generally efficacious and safe in treating various VM, LM, and some overgrowth conditions, particularly where PIK3CA mutations are present, including in PROS [10-12].…”

Section: Discussionmentioning

confidence: 99%

“…Clinical review was conducted every 2–3 months with phone consults between visits as needed. Duration of treatment needed in these conditions is not clear from the literature and varies for each patient [4].…”

Section: Discussionmentioning

confidence: 99%

“…Mosaicism and the timing of the mutation during development cause phenotypical variance, resulting in variable disease progression and overlapping features that make diagnosis difficult [2, 3]. Genetic research has shown the PI3K/AKT/mTOR pathway, especially the PIK3CA gene, and to a lesser degree the RAS/MAPK/MEK pathway play key roles in the regulation of angiogenesis, lymphangiogenesis, and cell growth [1, 3, 4]. Two overgrowth disorders associated with these pathways are congenital lipomatous overgrowth, VM, epidermal nevi, and spinal/skeletal anomalies syndrome (CLOVES) and epidermal nevus syndrome (ENS).…”

Section: Introductionmentioning

confidence: 99%

“…Treatment of overgrowth syndromes, LM, and VM is often difficult as few effective medical treatments exist and surgically removed growths can recur [10-13]. Gene elucidation has allowed for more targeted therapies, including novel medications and the repurposing of pre-existing medications such as sirolimus, an mTOR inhibitor, to be used, particularly where PIK3CA mutations are present [4, 10-12]. However, little evidence currently exists as to the efficacy of sirolimus in non-malignant somatic RAS mutation conditions.…”

Section: Introductionmentioning

confidence: 99%

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Lymphatic Malformation Responsive to Sirolimus in Keratinocytic Epidermal Nevus Syndrome with KRAS Mutation: A Case and Brief Literature Discussion

2021

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Lymphatic Malformation Responsive to Sirolimus in Keratinocytic Epidermal Nevus Syndrome with KRAS Mutation: A Case and Brief Literature Discussion

2021

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Barriers to Genetic Testing in Vascular Malformations

et al. 2023

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ImportanceVascular malformations (VMs) are rare disorders of vasculogenesis associated with substantial morbidity. Improved understanding of their genetic basis is increasingly guiding management, but logistical barriers to obtaining genetic testing in patients with VM may constrain treatment options.ObjectivesTo examine the institutional mechanisms for and obstacles to obtaining genetic testing for VM.Design, Setting, and ParticipantsThis survey study invited members of the Pediatric Hematology-Oncology Vascular Anomalies Interest Group, representing 81 vascular anomaly centers (VACs) serving individuals up to 18 years of age, to complete an electronic survey. Respondents were mostly pediatric hematologists-oncologists (PHOs) but included geneticists, genetic counselors, clinic administrators, and nurse practitioners. Responses that were received between March 1 and September 30, 2022, were analyzed with descriptive methods. Requirements for genetic testing by several genetics laboratories were also reviewed. Results were stratified by size of the VAC.Main Outcomes and MeasuresVascular anomaly center and associated clinician characteristics and practice patterns for ordering and obtaining insurance approval for genetic testing for VMs were collected.ResultsResponses were received from 55 of 81 clinicians, for a response rate of 67.9%. Most respondents were PHOs (50 [90.9%]). Most respondents (32 of 55 respondents [58.2%]) replied that they order genetic testing on 5 to 50 patients per year and reported a genetic testing volume increase of 2- to 10-fold over the past 3 years (38 of 53 respondents [71.7%]). Most testing was ordered by PHOs (35 of 53 respondents [66.0%]), followed by geneticists (28 [52.8%]) and genetic counselors (24 [45.3%]). In-house clinical testing was more common at large and medium-sized VACs. Small VACs were more likely to use oncology-based platforms, which potentially miss low-frequency allelic variants in VM. Logistics and barriers varied by size of the VAC. Obtaining prior authorization was the duty shared among PHOs, nurses, and administrative staff, but the burden of insurance denials and appeals were on PHOs (35 of 53 respondents [66.0%]). Lack of administrative support; unclear institutional, insurance, and laboratory requirements; and lack of clinician education were barriers to genetic testing at VACs of all sizes. The effort to obtain genetic testing for patients with VM, compared with patients with cancer, was perceived as excessive, despite genetic testing being considered standard of care for this population.Conclusions and RelevanceResults of this survey study showed the barriers to genetic testing for VM across VACs, described differences between VACs based on size, and proposed multiple interventions to support clinicians ordering genetic testing for VM. The results and recommendations should have broader application to clinicians caring for patients for whom molecular diagnosis is important to medical management.

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Venous malformation may be a feature of EXT1‐related hereditary multiple exostoses: A report of two unrelated probands

Albokhari

Bailey

Hwang

et al. 2023

American J of Med Genetics Pt A

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Hereditary multiple exostoses (HME), also known as hereditary multiple osteochondroma (HMO), is an autosomal dominant disorder caused by pathogenic variants in exostosin‐1 or ‐2 (EXT1 or EXT2). It is characterized by the formation of multiple benign growing osteochondromas (exostoses) that most commonly affect the long bones; however, it may also occur throughout the body. Although many of these lesions are clinically asymptomatic, some can lead to chronic pain and skeletal deformities and interfere with adjacent neurovascular structures. Here, we report two unrelated probands that presented with a clinical and molecular diagnosis of HME with venous malformation, a clinical feature not previously reported in individuals with HME.

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Vascular Anomalies

Cited by 71 publications

References 86 publications

Lymphatic Malformation Responsive to Sirolimus in Keratinocytic Epidermal Nevus Syndrome with KRAS Mutation: A Case and Brief Literature Discussion

Lymphatic Malformation Responsive to Sirolimus in Keratinocytic Epidermal Nevus Syndrome with KRAS Mutation: A Case and Brief Literature Discussion

Barriers to Genetic Testing in Vascular Malformations

Venous malformation may be a feature of EXT1‐related hereditary multiple exostoses: A report of two unrelated probands

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